PROJECT SUMMARY Screening for colorectal cancer (CRC) not only detects disease early but also prevents cancer by finding and removing precancerous polyps. The overall goal of our project, Accelerating Colorectal Cancer Screening and Follow-up through Implementation Science in Chicago (ACCSIS-Chicago), is to test a multilevel, multicomponent intervention to increase rates of CRC screening, follow-up, and referral-to-care among racial/ethnic minority and low income populations in Chicago, Illinois. In this project, we will include two different types of implementation strategies: 1) evidence-based multilevel, multicomponent intervention to increase rates of CRC screening, follow-up, and referral-to-care; and 2) implementation support strategies to support the implementation process that contribute to the adoption, implementation and sustainment of our proposed multilevel, multicomponent intervention. We will partner with 4 federally qualified health centers (FQHCs), which have 35 clinics in the Chicago area and provided primary care service to nearly 188,000 racial/ethnic minority and low income populations in 2016. During the UG3 Planning-Exploratory Phase, we will work with one of the 4 FQHC partners to pilot test, measure, and refine our proposed multilevel, multicomponent intervention in preparation for the experimental trial in the UH3 Implementation Phase, as well as assess the effectiveness of our implementation support strategies. In the UH3 Implementation Phase, we will use a stepped wedge cluster randomized trial design to examine the effectiveness and impact of our multilevel, multicomponent intervention on increasing rates of CRC screening, follow-up, and referral-to-care across our 4 partner FQHCs. The selection of our intervention components will be based on intensive literature review, and findings and lessons learned from our previous studies and projects. Our multilevel intervention components will include EMR provider reminders, provider assessment and feedback, patient navigation, provider education and community outreach. We will also test one local innovation, IL ColonCARES, during the UGH Phase to increase the rate of follow-up after a positive stool test among uninsured patients by linking uninsured patients with specialty services. We expect the finding from this study to have broad impact on understanding the implementation process to increase colorectal cancer screening, follow up, and referral to care across diverse health systems.